Nerve sparing feminizing genitoplasty with corporal septum excision in non-classic congenital adrenal hyperplasia

Abstract

Background/Aim: Non-classic congenital adrenal hyperplasia (CAH) is a milder form of CAH. The CYP21A2 gene is involved in the etiopathogenesis of both severe (classic) and mild (non-classic) form CAH, however, genetic mutations in non-classic CAH result in less impairment of 21-hydroxylase activity. Therefore, as in classic CAH, patients with non-classical CAH have no signs and symptoms of cortisol deficiency. Instead, there may be signs of hyperandrogenism that can appear later in childhood or in early adulthood. Due to excess androgenic effect on clitoris, labia minora, majora and the vagina, feminizing genitoplasty should be performed to make gender identities consistent and reshape the proper genital anatomy for sexual intercourse. However, there are few studies and controversy on feminizing genitoplasty procedures in adulthood. In this study, we aimed to design a new procedure to spare the nerves of the clitoris as well as the clitoral body, along with the cavernous tissue.
Methods: This is a case series of nine patients with a mean age of 24.8 years diagnosed with non-classic CAH who underwent feminizing genitoplasty, in which nerve-sparing clitoroplasty was performed with corporal septum excision by ventral approach. Initially, diagnostic cystoscopy was performed to detect the level of vaginal confluence into the urogenital sinus. The enlarged clitoris was degloved from 10 mm proximal to the glans up to the symphysis pubis. Corporal septum was excised from the ventral part of the clitoris up to the bifurcation of crura. Neurovascular bundle was preserved completely dorsally, and the clitoris was folded over itself and fixed at the level of crural bifurcation at 3 and 9 o'clock positions. Degloved clitoral preputium was used as Byars’ flaps for labiaplasty. A perineal inverted U incision was made and the vaginal introitus was enlarged with this flap. Female Genital Image Scale (FGIS) was used in the assessment of patients’ postoperative genital self-image.
Results: Feminizing genitoplasty (nerve-sparing clitoroplasty with corporal septum excision, labiaplasty and perineal flap vaginoplasty) was performed in nine patients diagnosed with non-classic CAH. The mean operation time was 112 minutes with a range of 90-140 minutes. Urogenital sinus mobilization was not performed as the vaginal confluence into urogenital sinus was low in cystoscopy. Patients were re-assessed at 1 month, 3 months and 6 months postoperatively. FGIS scores showed that four patients were “very satisfied,” one patient was “satisfied,” 2 patients were “moderately satisfied”, and one patient was “dissatisfied.” The maximum follow up was 2 years with no recorded short or long-term complications.
Conclusion: Nerve sparing clitoroplasty with corporal septum excision is a good option with satisfactory long term results for non-classic CAH patients. However, we need many more comparative studies to decide the gold standard method for optimal physiologic and cosmetic outcomes in CAH patients.

Full text

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Nerve sparing feminizing genitoplasty with corporal septum excision
in non-classic congenital adrenal hyperplasia
Adeviye Elçi Atılgan 1, Fatma Kılıç 2, Ali Acar 2, Tuğba Akçaoğlu 1, Asiye Uzun 1
How to cite: Atılgan AE, Kılıç F, Acar A, Akçaoğlu T, Uzun A. Nerve sparing feminizing genitoplasty with corporal septum excision in non-classic congenital adrenal
hyperplasia. J Surg Med. 2021;5(1):89-92.
J Surg Med. 2021;5(1):89-92. Research article
DOI: 10.28982/josam.865468
1 Istanbul Medipol University, Faculty of
Medicine, Department of Obstetrics and
Gynecology, Istanbul, Turkey
2 Necmettin Erbakan University, Meram Faculty
of Medicine, Department of Obstetrics and
Gynaecology, Konya, Turkey
ORCID ID of the author(s)
AEA: 0000-0003-4833-8978
FK: 0000-0002-9735-3552
AA: 0000-0001-6478-2206
TA: 0000-0002-0354-3292
AU: 0000-0001-8322-6643
Corresponding Author
Adeviye Elçi Atılgan
Istanbul Medipol University, Faculty of Medicine,
Department of Obstetrics and Gynecology,
İstanbul, Turkey
E-mail: dradeviye@gmail.com
󠄀
Ethics Committee Approval
Ethical committee approval was obtained from
Istanbul Medipol University, Faculty of Medicine
Ethical Committee (Aproval number: 36423-
11.08.2018).
All procedures in this study involving human
participants were performed in accordance with
the 1964 Helsinki Declaration and its later
amendments.
󠄀
Informed Consent
The authors stated that the written consent was
obtained from the patient presented with images
in the study.
󠄀
Conflict of Interest
No conflict of interest was declared by the
authors.
󠄀
Financial Disclosure
The authors declared that this study has received
no financial support.
󠄀
Published
2021 January 29
Copyright © 2021 The Author(s)
Published by JOSAM
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Abstract
Background/Aim: Non-classic congenital adrenal hyperplasia (CAH) is a milder form of CAH. The
CYP21A2 gene is involved in the etiopathogenesis of both severe (classic) and mild (non-classic) form
CAH, however, genetic mutations in non-classic CAH result in less impairment of 21-hydroxylase
activity. Therefore, as in classic CAH, patients with non-classical CAH have no signs and symptoms of
cortisol deficiency. Instead, there may be signs of hyperandrogenism that can appear later in childhood or
in early adulthood. Due to excess androgenic effect on clitoris, labia minora, majora and the vagina,
feminizing genitoplasty should be performed to make gender identities consistent and reshape the proper
genital anatomy for sexual intercourse. However, there are few studies and controversy on feminizing
genitoplasty procedures in adulthood. In this study, we aimed to design a new procedure to spare the
nerves of the clitoris as well as the clitoral body, along with the cavernous tissue.
Methods: This is a case series of nine patients with a mean age of 24.8 years diagnosed with non-classic
CAH who underwent feminizing genitoplasty, in which nerve-sparing clitoroplasty was performed with
corporal septum excision by ventral approach. Initially, diagnostic cystoscopy was performed to detect the
level of vaginal confluence into the urogenital sinus. The enlarged clitoris was degloved from 10 mm
proximal to the glans up to the symphysis pubis. Corporal septum was excised from the ventral part of the
clitoris up to the bifurcation of crura. Neurovascular bundle was preserved completely dorsally, and the
clitoris was folded over itself and fixed at the level of crural bifurcation at 3 and 9 o'clock positions.
Degloved clitoral preputium was used as Byars’ flaps for labiaplasty. A perineal inverted U incision was
made and the vaginal introitus was enlarged with this flap. Female Genital Image Scale (FGIS) was used
in the assessment of patients’ postoperative genital self-image.
Results: Feminizing genitoplasty (nerve-sparing clitoroplasty with corporal septum excision, labiaplasty
and perineal flap vaginoplasty) was performed in nine patients diagnosed with non-classic CAH. The
mean operation time was 112 minutes with a range of 90-140 minutes. Urogenital sinus mobilization was
not performed as the vaginal confluence into urogenital sinus was low in cystoscopy. Patients were re-
assessed at 1 month, 3 months and 6 months postoperatively. FGIS scores showed that four patients were
“very satisfied,” one patient was “satisfied,” 2 patients were “moderately satisfied”, and one patient was
“dissatisfied.” The maximum follow-up was 2 years with no recorded short or long-term complications.
Conclusion: Nerve sparing clitoroplasty with corporal septum excision is a good option with satisfactory
long-term results for non-classic CAH patients. However, we need many more comparative studies to
decide the gold standard method for optimal physiologic and cosmetic outcomes in CAH patients.
Keywords: Feminizing genitoplasty, Congenital adrenal hyperplasia, Clitoroplasty

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Introduction
Congenital adrenal hyperplasia (CAH) is the most
common sexual development disorder of individuals with 46XX
genotype [1]. The incidence of CAH is one in 15,000 newborns
[2]. A number of enzymatic defects in the production of cortisol
cause a shunting of cortisol precursors to an alternate metabolic
pathway, which results in an excess production of adrenal
androgens (i.e., DHEA, androstenedione, and testosterone). 21-
hydroxylase deficiency is the most common enzymatic defect,
and a wide array of clinical features can be observed according
to the level of impairment in cortisol and aldosterone
biosynthesis [3]. There are three clinical phenotypes as follows:
Classic salt-wasting (most severe), classic non-salt-wasting
(simple-virilizing), or non-classic (mild or late-onset). Non-
classic CAH is a milder form of the disease.
There is a close relationship between genotypic
CYP21A2 mutations and phenotype [4]. However, genetic
mutations associated with non-classical CAH result in less
impairment of 21-hydroxylase activity. In the most severe form,
concomitant aldosterone deficiency leads to salt wasting, while
patients with non-classic CAH do not have cortisol deficiency.
They have signs and symptoms of hyperandrogenism that are
seen later in childhood or early adulthood. Although it is a milder
form of the disease, they cannot have sexual intercourse without
a feminizing genitoplasty procedure. Hirsutism, clitoromegaly,
voice thickening, masculine muscle structure are other important
problems of non-classic CAH female patients. The main aim of
treatment in female patients with mild or non-classic CAH is
controlling excess androgen and transforming its virilizing effect
to feminizing. However, the surgical method for feminizing
genitoplasty is controversial. We aimed to share our experience
on nerve sparing feminizing genitoplasty with corporal septum
excision in non-classic CAH patients.
Materials and methods
We retrospectively reviewed the files of nine female
patients diagnosed with mild CAH who underwent feminizing
genitoplasty at two university hospitals between 2012-2020. All
patients were married with a mean age of 24.8 years (range: 21 -
32 years) and presented with enlarged clitoris with inability to
have sexual intercourse. Physical exam revealed clitoromegaly,
vaginal stenosis and increased perianal distance (Figure 1). The
uterus and ovaries were normal in pelvic ultrasound.
Chromosome analysis was performed in all patients and resulted
as 46XX. Their medical therapy was planned by an
endocrinologist. They did not start cortisol replacement, and
instead, Spironolactone, an aldosterone antagonist, was
administered for its anti-androgenic effect. Ethinylestradiol and
cyproterone acetate combination was added to medical therapy to
speed up the regression of the virilizing signs and symptoms.
Ethical committee approval was obtained from Istanbul Medipol
University, Faculty of Medicine Ethical Committee (Approval
number: 36423-11.08.2018). All patients read and signed the
informed consent forms.
Surgical technique
All patients were operated under general anesthesia and
the procedure began with diagnostic cystoscopy to exclude high
confluence of urogenital sinus. Then, a 14F urinary catheter was
inserted into the bladder, and the perianal trigone was marked
with a sterile pencil (Figure 2a). A stay suture was placed for
traction at the 12 o’clock position on the glans (Figure 2b). A
circumcisional incision was made 10 mm proximal to the glans
dorsally and 2 mm ventrally all around the shaft. The clitoris was
degloved from 10 mm proximal to the corona up to the
symphysis pubis (Figure 2c). Corporal septum was excised
ventrally up to the bifurcation of crura (Figure 2d).
Neurovascular bundle was preserved completely dorsally. The
clitoris was folded over itself and fixed at the level of crural
bifurcation at 3 and 9 o'clock positions (Figure 2e). Degloved
clitoral preputium was used as Byars’ flaps for labia minora
reconstruction (Figure 2f). Then, a perineal inverted U incision
was made, with which the vaginal introitus was enlarged (Figure
2g). A vaginal tamponade with estrogen cream was inserted into
the vagina (Figure 2h).
Figure 1: Preoperative appearance of the external genitalia of a non-classic CAH patient
Figure 2: Step by step nerve sparing feminizing genitoplasty with corporal septum excision
procedure
Patients were hospitalized for two nights. Control
examinations were performed at one week, six weeks and three
months postoperatively. Vaginal mold tamponade and urethral
catheter were removed at the control examination at the first
postoperative week. Female Genital Image Scale (FGIS),
including 12 items, was used for the patients to rate their genital
satisfaction along a five-point Likert-type scale from 1 = “Very
satisfied” to 5 = “Very dissatisfied” at the control examination at
three months postoperatively [5].
Results
Feminizing genitoplasty (nerve sparing clitoroplasty
with corporal septum excision, labiaplasty and perineal flap
vaginoplasty) was performed in nine patients diagnosed with
non-classic CAH. The mean operation time was 112 minutes
with a range of 90-140 minutes. Urogenital sinus mobilization
was not performed as the vaginal confluence into urogenital
sinus was low at cystoscopy. Preoperative mean clitoral size was
7.2 cm (6.8 cm-8.8 cm), which decreased to a mean of 2.3 cm
(1.2 cm-2.6 cm) postoperatively. All patients started sexual

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P a g e | 91
activity 8 weeks later. FGIS scale scores obtained three months
later showed that four patients were “very satisfied,” one patient
was “satisfied,” two patients were “moderately satisfied,” and
one patient was “dissatisfied” (Table 1). The mean follow-up
period was 13 months with a range of 8 to 26 months. There
were no significant short- or long-term complications.
Table 1: Patients’ FGIS scale scores
FGIS scale
n (%)
1-Very Satisfied
4(44.4)
2- Satisfied
1(11.1)
3-Moderate
2(22.2)
4-Dissatisfied
1(11.2)
5-Very Dissatisfied
1(11.1)
Discussion
Females with classic CAH are usually diagnosed at birth
with noticeable penis-like appearance of the clitoris. In-utero
exposure of excess fetal adrenal androgens lead to clitoral
enlargement. On the other hand, females with non-classic CAH
are not diagnosed so early. They are usually diagnosed later in
childhood or early adulthood. Most cases are referred to the
physicians due to inability to have sexual intercourse when they
get married. Their internal genitalia are anatomically female, and
they have regular or irregular menstrual cycles. Their phenotype
is influenced by the severity of the CYP21A2 mutations and 21-
hydroxylase enzyme defect, leading to virilization of the external
genitalia at varying levels. Physicians should be informed about
the other conditions that can cause enlargement of the clitoris,
such as exogenous in-utero androgen exposure due to the
pregnant mother suffering from masculinizing tumors such as
arrhenoblastoma [Ovarian Sertoli-Leydig cell tumors (SLCTs)]
of the ovary or exogenous topical androgen use [6-8]. Some
reports state that clitoral enlargement can be secondary to
neurofibromatosis [9]. Another important condition causing
idiopathic clitoromegaly in females is prematurity [10].
The main purpose of feminizing genitoplasty procedure
is providing a proper width vaginal introitus and decreasing
clitoral size to obtain a feminine genital appearance. It is
documented in some studies that the clitoral length may vary
according to ethnicity, like penile length [11]. However, the
normal range for each ethnic race is not determined precisely.
Considering our country, the mean clitoral length of Turkish
newborns was reported as 4.93 (1.61) mm in a research [12]. Our
study populations’ preoperative mean clitoral length was 7.2 cm.
The clitoris is attached by the suspensory ligament to the front of
the symphysis pubis]. However, the size of free part varies
considerably as it has cavernous tissue [13]. For example, the
clitoral body is 1–3 cm long in the flaccid state [14]. A physician
first suspects clitoromegaly on physical examination. It is
currently defined as a clitoris longer than 1 cm in newborns [15].
Parity can also affect clitoral size but age, body mass index and
oral contraceptive use do not [16]. The most important step while
reducing clitoral size is to preserve the neurovascular bundle of
the clitoris. Poppas et al. described the nerve sparing ventral
clitoroplasty procedure [17]. They examined the nerves in situ
using optical coherence technology. Many women who
underwent infant genitoplasty in 1980s were mutilated because
the importance of clitoral sensation was not known at the time
[18]. Old surgical techniques are no longer used, while nerve-
sparing clitoroplasty has become widely adopted since the 2000s.
The infants operated with old techniques report decreased
sensation of the clitoris, and some of them are anorgasmic [19].
One study found the rate of anorgasmia to be as high as 40%
[20]. Extensive clitoral resection should not be performed. A
clear understanding of clitoral anatomy is important for surgical
reconstruction. As in the human penis, nerves in the clitoris form
an extensive network around the tunica of the dorsal corporeal
body. The nerve-free zone is found in the midline, at 12 o'clock
position [21]. For this reason, operation starts with a traction
suture placed on clitoral glans at 12 o’clock. Nowadays, more
effort is made to preserve nerves, which we also hoped to
achieve with dorsal nerve-sparing clitoroplasty. In addition, we
did not completely remove the corpus cavernosum ventrally. The
human clitoris has two corporeal bodies that are smaller but
analogous with the penis. A fibrous midline septum exists on the
ventral aspect and extends approximately halfway into the glans
[21]. We tried to excise this septum to be able to fold the clitoris
over itself, hence decreasing clitoral size while preserving the
corporal body.
To the best of our knowledge, this is the first study
reporting dorsal nerve-sparing clitoroplasty performed on non-
classic CAH adult females, because most studies are conducted
on classic CAH during the newborn or childhood period. We
could assess patients’ postoperative cosmetic and functional
outcomes with FGIS more clearly as they were all sexually
active adults. There were two major limitations to this study. One
was the small sample size and the other, lack of a control group.
Conclusion
Nerve sparing clitoroplasty with corporal septum
excision may be a good option with satisfactory long-term results
for non-classic CAH patients. However, we need more
comparative, multicenter studies to determine a gold standard
method for achieving the optimal physiologic and cosmetic
outcome in CAH patients. In the future, we hope to improve
surgical techniques to preserve the corporal body in addition to
nerve bundle.
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